Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

BMC Neuroscience

Research Article

László Héja¹  Tünde Molnár¹  Julianna Kardos¹  Gabriella Nyitrai¹  Péter Barabás²  Zsuzsa Emri³  Miklós Palkovits⁴  Árpád Dobolyi⁴ 

[1] Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeriút 59-67, 1025, Budapest, Hungary;Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeriút 59-67, 1025, Budapest, Hungary;Department of Ophthalmology, University of Utah, 65 Mario Capecchi Drive, 84132, Salt Lake City, UT, USA;Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeriút 59-67, 1025, Budapest, Hungary;Department of Zoology, Eszterházy Károly College, Leányka utca 6, 3300, Eger, Hungary;Neuromorphological and Neuroendocrine Research Laboratory, Semmelweis University and Hungarian Academy of Sciences, Tűzoltó utca 58, 1094, Budapest, Hungary;

关键词: Glial Fibrillary Acidic Protein;    P2Y1 Receptor;    Bergmann Glia;    Cx43 Protein;    Flufenamic Acid;   

DOI  :  10.1186/1471-2202-12-96

 received in 2011-06-28, accepted in 2011-10-03,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundAccumulating evidence suggests that glial signalling is activated by different brain functions. However, knowledge regarding molecular mechanisms of activation or their relation to neuronal activity is limited. The purpose of the present study is to identify the characteristics of ATP-evoked glial signalling in the brain reward area, the nucleus accumbens (NAc), and thereby to explore the action of citric acid cycle intermediate succinate (SUC).ResultsWe described the burst-like propagation of Ca2+ transients evoked by ATP in acute NAc slices from rat brain. Co-localization of the ATP-evoked Ca2+ signalling with immunoreactivities of the astroglia-specific gap junction forming channel protein connexin43 (Cx43) and the glial fibrillary acidic protein (GFAP) indicated that the responsive cells were a subpopulation of Cx43 and GFAP immunoreactive astrocytes. The ATP-evoked Ca2+ transients were present under the blockade of neuronal activity, but were inhibited by Ca2+ store depletion and antagonism of the G protein coupled purinergic P2Y1 receptor subtype-specific antagonist MRS2179. Similarly, Ca2+ transients evoked by the P2Y1 receptor subtype-specific agonist 2-(Methylthio)adenosine 5'-diphosphate were also blocked by MRS2179. These characteristics implied that intercellular Ca2+ signalling originated from the release of Ca2+ from internal stores, triggered by the activation of P2Y1 receptors. Inhibition by the gap junction blockers carbenoxolone and flufenamic acid and by an antibody raised against the gating-associated segment of Cx43 suggested that intercellular Ca2+ signalling proceeded through gap junctions. We demonstrated for the first time that extracellular SUC also evoked Ca2+ transients (EC50 = 50-60 μM) in about 15% of the ATP-responsive NAc astrocytes. By contrast to glial cells, electrophysiologically identified NAc neurons surrounded by ATP-responsive astrocytes were not activated simultaneously.ConclusionsWe concluded, therefore, that ATP- and SUC-sensitive Ca2+ transients appear to represent a signalling layer independent of NAc neurons. This previously unrecognised glial action of SUC, a major cellular energy metabolite, may play a role in linking metabolism to Ca2+ signalling in astrocytic networks under physiological and pathological conditions such as exercise and metabolic diseases.

【 授权许可】

Unknown   
© Molnár et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.